Pharmacokinetics and Bioequivalence Studies of an Investigational Oral Formulation of Edaravone (MT-1186)


Clinical Trials

Poster Number: 30


Stephen Apple, MD, Mitsubishi Tanabe Pharma America, Inc., Hidetoshi Shimizu, Mitsubishi Tanabe Pharma Corporation, Manabu Hirai, MS, Mitsubishi Tanabe Pharma Corporation, Yukiko Nishimura, Mitsubishi Tanabe Pharma Corporation

Background: Radicava® (edaravone injection) is a US FDA-approved treatment for amyotrophic lateral sclerosis (ALS) that slows the rate of physical functional decline. As intravenous (IV) administration can burden patients, orally administered treatments are needed.
Objectives: To assess the pharmacokinetics (PK) and bioequivalence of investigational oral edaravone (MT-1186) compared with IV edaravone.
Results: Three open-label, phase 1 clinical studies were conducted. Study J03 was a single-dose, crossover, bioequivalence study involving 42 healthy subjects who received 105 mg of oral edaravone and IV edaravone (60 mg/60 minutes). PK parameters, metabolic profiles, and elimination pathways were assessed. The 24-hour PK of a single dose of oral edaravone was assessed in 9 patients with ALS (Study J04) and 6 patients with ALS with percutaneous endoscopic gastrostomy (PEG) tubes (Study J05).
The findings from Study J03 showed similar plasma concentration-time profiles for oral edaravone and IV edaravone. The 105-mg oral suspension of edaravone demonstrated equivalent plasma exposure to the 60-mg IV formulation. One subject in each group experienced an adverse event (AE)—both mild in severity and not related to edaravone, as determined by the investigator.
In Study J04, 105 mg oral edaravone was well absorbed and well tolerated, with 1 treatment-emergent AE (n=1) reported as mild in severity and not reasonably related to the investigational product, as determined by the investigator.
In Study J05, results obtained after the administration of 105 mg of edaravone oral suspension via gastric fistula in patients with ALS who had PEG tubes were similar to Study J04.
Conclusions: In healthy volunteers, PK bridging was confirmed from IV edaravone to oral edaravone. The PK profile of oral edaravone was similar between patients with ALS with and without PEG. AEs were mostly representative of ALS progression, and the safety results were generally consistent with the safety profile of IV edaravone.